Available commercial Rotavirus liquid oral vaccines are required to be stored under refrigerated conditions. This constitutes a significant logistic issue when the vaccine is needed in areas where refrigeration is not widely available. Furthermore, the vaccines are not sufficiently stable to resist further manufacturing processes that may be involved in final dosage presentations.
Rotaviruses can cause acute gastroenteritis, which frequently requires hospitalization of infants and young children in developed countries, and is a common cause of death in children less than 5 years of age in developing regions of the world. Studies in the developed world have demonstrated that between 34 and 63% of hospitalizations of children for acute diarrheal disease are associated with Rotavirus infection. Rotaviruses are also responsible for substantial proportion of the mortality associated with diarrheal diseases in third world countries. An effective Rotavirus vaccine would therefore have a major impact on the health of children in both the developed and developing areas of the world.
Rotaviruses are double stranded RNA viruses with an inner and outer capsid. Several serotypes have been defined by plaque reduction neutralization tests, and studies of reassortant viruses have demonstrated that two outer capsid proteins, VP7 and VP4, are the determinants of virus serotype. The gene segments encoding the VP7 and VP4 proteins segregate independently, so it has been proposed that serotyping nomenclature should include both the G type, determined by VP7, and the P type, determined by VP4. Most human rotavirus infections in the U.S. are caused by viruses of G types 1, 2, 3, or 4, and P types 1, 2, or 3. However, other human rotavirus types, including for example, type G9, are more prevalent in Asia, Europe and certain third world countries.
In U.S. Pat. No. 6,616,931, Rotavirus Vaccine Formulations, to Burke, et al., liquid and lyophilized formulations of vaccines against rotavirus infection and methods of their preparation were described. The formulations include sugars and buffering agents appropriate for oral administration of Rotavirus vaccines. For some serotypes, Burke has found Rotaviruses can remain viable longer in liquid formulations containing about 50% of sugars, a phosphate buffer, and a carboxylate, at about neutral pH. For some serotypes, Burke has found Rotaviruses can remain viable longer in lyophilized cakes dried from formulations containing about 5% of sugars, a phosphate buffer and human serum albumin. However, Burke teaches that the presence of zinc ions dramatically reduce the viability of Rotaviruses in the presence or absence of calcium ions.
In view of the above, a need exists for liquid Rotavirus live vaccines that remain viable for extended periods at room temperature. It would be desirable to have methods of Rotavirus vaccination that allow the vaccine to retain additional viability in transport and storage. The present invention provides these and other features that will be apparent upon review of the following.